Prostate cancer imaging of FSHR antagonist modified with a hydrophilic linker

Follicle-stimulating hormone receptor (FSHR) is selectively expressed in endothelial cells of prostate cancer (PCa) and becomes a potential target for tumor diagnosis and therapy. (18)F-Al-NOTA-MAL-FSH1 is a promising PET imaging probe for targeting FSHR; however, the unfavorable abdominal backgrounds may hamper clinical translation. GGGRDN is a new hydrophilic linker, which can improve the imaging quality of radiolabeled peptides. In this study, GGGRDN-FSH1 (denoted as FSH2) was designed and conjugated with NOTA-MAL for (18)F-Al radiolabeling. NOTA-MAL-FSH2 was obtained with about 50% yield and labeled using (18)F-Al in a one-step method within 20 min with a yield of 41.46 ± 10.36% (non-decay-corrected). The radiochemical purity was more than 95% and the specific activity was more than 50 GBq/µmol. The in vitro stability studies were determined in PBS and human serum. (18)F-Al-NOTA-MAL-FSH2 remained stable in PBS and human serum. Balb/c nude mice bearing PC-3 human PCa were used for in vivo study. PC-3 tumors were clearly visualized with good contrast to background through microPET. ROI analysis showed the tumor uptake values were 2.68 ± 0.52 and 1.97 ± 0.61%ID/g at 30 and 60 min post injection (p.i.), respectively. Biodistribution studies showed that the accumulations of (18)F-Al-NOTA-MAL-FSH2 in liver and intestine were 0.47 ± 0.11 and 0.12 ± 0.03%ID/g respectively at 60 min p.i. FSHR-binding specificity was also demonstrated by reduced tumor uptake after coinjection of excessive unlabeled FSH2. In conclusion, (18)F-Al-NOTA-MAL-FSH2 was successfully prepared in a one-step method and showed better pharmacokinetics than (18) F-Al-NOTA-MAL-FSH1. Favorable preclinical study revealed that (18)F-Al-NOTA-MAL-FSH2 appears to be a promising candidate for FSHR-positive tumor imaging.